Heparin resistance (HR), defined as a decrease in heparin responsiveness, can result in adverse events with prolonged duration of surgery. Although some clinical risk factors have been suggested, the relationship with the surgical diagnosis is unclear. The aim of present study was to elucidate the clinical predictors of HR including the surgical diagnosis.This retrospective cohort study determined the incidence of HR (defined as activated clotting time [ACT] <400 seconds after 250-350 IU/kg of heparin administration) and heparin sensitivity index (HSI) was calculated from the rate of change in ACT per heparin dose. Preoperative demographic data, medication history, and laboratory data also were analyzed.Single institution, tertiary care hospital.Adult patients who underwent cardiovascular surgery with cardiopulmonary bypass between January 2012 and September 2018.None.Of 287 patients, 88 (30.7%) were classified as HR. In univariate analysis, infective endocarditis (IE), platelet count, and serum fibrinogen and albumin levels were associated with HR. After adjustment for baseline ACT and initial heparin dose, IE (odds ratio 4.57, [95% CI: 1.10-19.1]; p = 0.037) and albumin ≤3.5 g/dL (3.17, [1.46-6.93]; p = 0.004) were associated independently with HR. Patients with IE had significantly lower HSI than those with other diseases. All HR patients were treated with additional heparin, and 17 of them received human antithrombin-III concentrate.Infective endocarditis and preoperative hypoalbuminemia were associated independently with HR. The optimal anticoagulation strategy for patients with these risk factors requires further investigations based on the authors' findings.